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Clonal abnormalities may serve as diagnostic tool for blood cancers
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Clonal cytopenias of undetermined significance occurred more frequently than myelodysplastic syndrome in patients with cytopenias, suggesting they should be part of the diagnostic criteria for recognized blood cancers.
Further, clonal cytopenias of undetermined significance (CCUS) appeared common among older patients with low blood counts.
It is difficult to establish a diagnosis in patients suspected of having myelodysplastic syndrome (MDS), and the identification of somatic mutations could help aid in diagnosis, researchers wrote.
Rafael Bejar, MD, PhD, assistant professor of medicine at University of California, San Diego’s Moores Cancer Center, and colleagues conducted a prospective study to examine the frequency and types of mutations in patients with unexplained cytopenias.
The researchers studied the bone marrow of 144 patients with at least one unexplained, clinically meaningful cytopenia. They diagnosed 24 (17%) with MDS, 21 (15%) with idiopathic cytopenias of undetermined significance (ICUS), with some evidence of dysplasia, and 99 (69%) with ICUS and no dysplasia.
They then sequenced bone marrow DNA for mutations in 22 frequently mutated myeloid malignancy genes.
Somatic mutations could be identified in 71% of patients diagnosed with MDS, 62% of patients with ICUS and some degree of dysplasia, and 20% of patients with ICUS and no dysplasia.
Forty-two patients (35%) with ICUS carried either a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis, suggesting CCUS.
The researchers validated these findings in a cohort of 340 patients with lower-risk MDS (n = 91) or ICUS (n = 249).
In this cohort, mutations occurred in 79% of patients with MDS, 45% of patients with ICUS and some degree of dysplasia, and 17% of patients with ICUS and no dysplasia (P < .0001). When clonal chromosomal abnormalities were included, 38% of patients had evidence of clonal hematopoiesis indicative of CCUS.
The researchers described the mutated cells in patients with CCUS as bone marrow polyps. They believed that these polyps may be precursors of blood cancers, such as MDS or acute myeloid leukemia.
With the exception of SF3B1 — which rarely occurred in patients with ICUS and no dysplasia — the spectrum of mutated genes appeared similar across disease categories.
Mean age, blood counts and variant allele fractions appeared similar among patients with MDS or CCUS.
The researchers acknowledged a lack of follow-up as a study limitation.
“We do not know to what extent patients who have low blood counts and mutations are at increased risk for developing an overt malignancy,” Bejar said in a press release. “We hope that by defining CCUS, future studies will follow these patients to learn what these mutations mean for their future as their genetically abnormal cells may represent early stages of subsequent blood cancers.” – by Cameron Kelsall
Disclosure: Genoptix provided funding for this study. Bejar reports a licensing agreement with Genoptix for intellectual property. Other researchers report consultant and/or employment with Genoptix, as well as consultant roles with Celgene.
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